Genetic Variant XYLB:c.1533+14G>A (chr3-38400999-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005108.4(XYLB):c.1533+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,611,952 control chromosomes in the GnomAD database, including 226,652 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 16049 hom., cov: 32)

Exomes 𝑓: 0.53 ( 210603 hom. )

Consequence

XYLB
NM_005108.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.713

Publications

26 publications found

Variant links:

Genes affected

XYLB (HGNC:12839): (xylulokinase) The protein encoded by this gene shares 22% sequence identity with Hemophilus influenzae xylulokinase, and even higher identity to other gene products in C.elegans (45%) and yeast (31-35%), which are thought to belong to a family of enzymes that include fucokinase, gluconokinase, glycerokinase and xylulokinase. These proteins play important roles in energy metabolism. [provided by RefSeq, Aug 2009]

XYLB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XYLB	NM_005108.4 link	c.1533+14G>A		intron_variant	Intron 18 of 18	ENST00000207870.8	NP_005099.2	O75191-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XYLB	ENST00000207870.8 link	c.1533+14G>A		intron_variant	Intron 18 of 18	1	NM_005108.4	ENSP00000207870.3		O75191-1

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65562

AN:

151986

Hom.:

16051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.494

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.451

GnomAD2 exomes

AF:

0.475

AC:

119278

AN:

251274

AF XY:

0.488

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.333

Gnomad ASJ exome

AF:

0.501

Gnomad EAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.529

Gnomad NFE exome

AF:

0.564

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

AF:

0.530

AC:

774181

AN:

1459848

Hom.:

210603

Cov.:

AF XY:

0.531

AC XY:

385811

AN XY:

726368

show subpopulations

African (AFR)

AF:

0.197

AC:

6598

AN:

33434

American (AMR)

AF:

0.339

AC:

15147

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

12950

AN:

26118

East Asian (EAS)

AF:

0.302

AC:

12000

AN:

39684

South Asian (SAS)

AF:

0.518

AC:

44625

AN:

86198

European-Finnish (FIN)

AF:

0.536

AC:

28594

AN:

53396

Middle Eastern (MID)

AF:

0.479

AC:

2757

AN:

5760

European-Non Finnish (NFE)

AF:

0.560

AC:

621415

AN:

1110230

Other (OTH)

AF:

0.499

AC:

30095

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

18360

36720

55079

73439

91799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17058

34116

51174

68232

85290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.431

AC:

65570

AN:

152104

Hom.:

16049

Cov.:

AF XY:

0.428

AC XY:

31847

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.210

AC:

8719

AN:

41478

American (AMR)

AF:

0.387

AC:

5919

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.494

AC:

1714

AN:

3472

East Asian (EAS)

AF:

0.270

AC:

1395

AN:

5168

South Asian (SAS)

AF:

0.506

AC:

2437

AN:

4820

European-Finnish (FIN)

AF:

0.526

AC:

5559

AN:

10572

Middle Eastern (MID)

AF:

0.479

AC:

140

AN:

292

European-Non Finnish (NFE)

AF:

0.564

AC:

38314

AN:

67988

Other (OTH)

AF:

0.450

AC:

951

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1769

3538

5308

7077

8846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.507

Hom.:

65974

Bravo

AF:

0.406

Asia WGS

AF:

0.399

AC:

1386

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.51

(source)

DANN

Benign

0.47

PhyloP100

-0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over